Plasma LECT2 Level And Its Correlation With Insulin Resistance In Patients With Type 2 Diabetes Mellitus And Obesity

Research BackgroundIn China,diabetes mellitus and obesity have become chronic diseases endangering public health,of which the prevalence rates have shown rapidly developing trend.Caused by multiple etiological factors,such as heredity and environment,diabetes mellitus is a type of metabolic disorders characterized by chronic hyperglycemia.Overweight and obesity significantly increase the prevalence rate of pre-diabetes and diabetes.The main manifestations of type 2 diabetes mellitus are pancreatic ?-cell dysfunction and insulin resistance.As the common feature of type 2 diabetes and obesity,insulin resistance manifests mainly as hyperinsulinemia.At the early stage of diabetes,targeting the pathophysiological defects can effectively regulate the blood glucose profiles and improve insulin resistance so as to delay the disease progression.With more and more study focused on the mechanisms about adipose tissue,muscular tissue and liver participating in regulating energy metabolic homeostasis,it has been proved that liver can secrete many kinds of liver-derived proteins named hepatokines involved in glycolipid metabolism,which can accelerate or delay the occurrence and development of insulin resistance.Coded by human LECT2 gene,LECT2(leukocyte cell-derived chemotaxin 2,LECT2)is a newly discovered hepatokine,which is mainly expressed in the hepatocytes and secreted into peripheral blood.The recent research has shown that the regulation of LECT2 in glycometabolism could play an important role in modulating insulin sensitivity.However,most of the existing studies were still in the basic research phase,and there were few clinic studies.As insulin resistance is one of the important pathogenesis of type 2 diabetes and obesity,to study the relationship between circulating LECT2 level with blood glucose,lipid profiles and insulin resistance may be the breakthrough point to discover the role of LECT2 participating in glycolipid metabolism and occurrence development of type 2 diabetes mellitus and obesity.ObjectivesTo observe the changes in levels of plasma leukocyte cell-derived chemotaxin 2(LECT2)in patients with newly diagnosed type 2 diabetes and normal subjects with different body mass index,and to analyze the relationship between the level of plasma leukocyte derived chemokine 2(LECT2)and glycolipid metabolism and insulin resistance.To investigate the effect of leukocyte cell-derived chemotaxin 2(LECT2)in the occurrence and development of type 2 diabetes mellitus and obesity.MethodsA number of 173 subjects as research objects were recruited from January 2016 to December 2016 in Zhujiang Hospital of Southern Medical University,among which there were 93 newly diagnosed type 2 diabetics,and we chose 80 aged-and sex-matched healthy controls as normal control group.Furtherly,on the basis of body mass index(BMI?24kg/m2)as pointcut,we separately divided type 2 diabetes group and normal control group into two subgroups,normal weight(BMI<24kg/m2).subgroup and overweight/obesity subgroup(BMI?24kg/m2).Demographics and medical history were recorded.Anthropometric indexes including body height,weight,blood pressure,waist circumference and hip circumference were measured,whereby body mass index(BMI)and waist-to-hip ratio(WHR)were calculated.Blood samples were collected after 8 hours of fasting for the assessment of fasting plasma glucose(FPG),fasting insulin(FIns),C peptide,HbAlc,hypersensitive C-reactive protein(hs-CRP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),serum creatinine(Scr),triglycerides(TG),total cholesterol(TC),low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol(HDL-C)and Uric acid(UA).Applying Homeostasis Model Assessment to calculate HOMA-IR index to assess insulin resistance,and to calculate HOMA-%? index to assess pancreatic islet ?-cell secretion function.The level of plasma LECT2 and Fetuin-A was determined by ELISA.Results1.The concentrations of plasma LECT2 in patients with newly diagnosed T2DM were significantly higher than that in normal control group[(30.30±9.64)ng/ml vs.23.23±5.23]ng/ml,P<0.01).The concentrations of plasma LECT2 in overweight and obese patients were significantly higher than that in normal weight subjects.The concentrations of plasma LECT2 in abdominal obesity group were significantly higher than that in non-abdominal obesity group(all P<0.05).2.The partial correlation analysis showed that LECT2 concentration was positively correlated with FPG,FIns,C peptide,HbAlc,AST,TG,HOMA-IR,Fetuin-A after the adjustment of age,gender and BMI,while was negatively correlated with HDL-C,HOMA-%? and QUICKI(all P<0.05).Multivariate regression analysis showed that levels of HDL-C,HOMA-IR,BMI,Fins and TG were important factors affecting plasma LECT2 level.3.Binary Logistic regression analysis revealed that individuals with higher expression level of plasma LECT2 might have higher risk of T2DM and obesity,and the adjusted OR value was separately 1.15 and 1.11.4.The ROC curve suggested that the optimal cut-off value of plasma LECT2 to predict T2DM was 28.75ng/ml,and the area under the ROC curve was 0.721(95%CI 0.65-0.78,P<0.01),the sensitivity was 51.6%and the specificity was 86.2%.ConclusionsThe concentrations of plasma LECT2 in T2DM and obesity patients were both higher than that in normal controls and were closely related with glycolipid metabolism and insulin resistance.High level of LECT2 was the risk factor for T2DM and obesity,which might play an important role in the occurrence and development of T2DM and obesity.